Typhim

"The U.S. Food and Drug Administration today approved Bexsero, a vaccine to prevent invasive meningococcal disease caused by Neisseria meningitidis serogroup B in individuals 10 through 25 years of age.

SIDE EFFECTS

Data From Clinical Trials

Because clinical trials are conducted under widely
varying conditions, adverse reactions rates observed in the clinical trials of
a vaccine cannot be directly compared to rates in the clinical trials of
another vaccine and may not reflect the rates observed in practice. The adverse
reaction information from clinical trials does, however, provide a basis for
identifying the adverse events that appear to be related to vaccine use and for
approximating rates.

Safety of Typhim Vi vaccine, the US licensed liquid
formulation, has been assessed in clinical trials in more than 4,000 subjects
both in countries of high and low endemicity. In addition, the safety of the
lyophilized formulation has been assessed in more than 6,000 individuals. The adverse
reactions were predominately minor and transient local reactions. Local
reactions such as injection site pain, erythema, and induration almost always
resolved within 48 hours of vaccination. Elevated oral temperature, above 38°C
(100.4°F), was observed in approximately 1% of vaccinees in all studies. No serious
or life-threatening systemic events were reported in these clinical trials.10,11

Adverse reactions from two trials evaluating Typhim Vi
vaccine lots in the US (18- to 40-year-old adults) are summarized in Table 3.
No severe or unusual side effects were observed. Most subjects reported pain
and/or tenderness (pain upon direct pressure). Local adverse experiences were
generally limited to the first 48 hours.10,11

Table 310,11: PERCENTAGE OF 18- TO
40-YEAR-OLD US ADULTS PRESENTING WITH LOCAL OR SYSTEMIC REACTIONS WITHIN 48
HOURS AFTER THE FIRST IMMUNIZATION WITH TYPHIM Vi VACCINE

REACTION

Trial 1 Placebo
N = 54

Trial 1 Typhim Vi vaccine
N = 54 (1 Lot)

Trial 2 Typhim Vi vaccine
N = 98 (2 Lots combined)

Local

Tenderness

7 (13.0%)

53 (98.0%)

95 (96.9%)

Pain

4 (7.4%)

22 (40.7%)

26 (26.5%)

Induration

0

8 (14.8%)

5 (5.1%)

Erythema

0

2 (3.7%)

5 (5.1%)

Systemic

Malaise

8 (14.8%)

13 (24.0%)

4 (4.1%)

Headache

7 (13.0%)

11 (20.4%)

16 (16.3%)

Myalgia

0

4 (7.4%)

3 (3.1%)

Nausea

2 (3.7%)

1 (1.9%)

8 (8.2%)

Diarrhea

2 (3.7%)

0

3 (3.1%)

Feverish (subjective)

0

6 (11.1%)

3 (3.1%)

Fever ≥ 100°F

0

1 (1.9%)

0

Vomiting

0

1 (1.9%)

0

No studies were conducted in US children. Adverse
reactions from a trial in Indonesia in children one to twelve years of age are
summarized in Table 4.10,11 No severe or unusual side effects were
observed.

Table 410,11: PERCENTAGE OF INDONESIAN
CHILDREN ONE TO TWELVE YEARS OF AGE PRESENTING WITH LOCAL OR SYSTEMIC REACTIONS
WITHIN 48 HOURS AFTER THE FIRST IMMUNIZATION WITH TYPHIM Vi VACCINE

REACTIONS

N = 175

Local

Soreness

23 (13.0%)

Pain

25 (14.3%)

Erythema

12 (6.9%)

Induration

5 (2.9%)

Impaired Limb Use

0

Systemic

Feverishness*

5 (2.9%)

Headache

0

Decreased Activity

3 (1.7%)

* Subjective feeling of fever.

In the US Reimmunization Study, subjects who had received
Typhim Vi vaccine 27 or 34 months earlier, and subjects who had never
previously received a typhoid vaccination, were randomized to placebo or Typhim
Vi vaccine, in a double-blind study. Safety data from the US Reimmunization
Study are presented in Table 5.10,11,13 In this study 5/30 (17%)
primary immunization subjects and 10/45 (22%) reimmunization subjects had a
local reaction. No severe or unusual side effects were observed. Most subjects
reported pain and/or tenderness (pain upon direct pressure). Local adverse
experiences were generally limited to the first 48 hours.10,11,13

Table 510,11,13: US REIMMUNIZATION STUDY,
SUBJECTS PRESENTING WITH LOCAL AND SYSTEMIC REACTIONS WITHIN 48 HOURS AFTER IMMUNIZATION
WITH TYPHIM Vi VACCINE

REACTION

PLACEBO
(N = 32)

FIRST IMMUNIZATION
(N = 30)

REIMMUNIZATION
(N = 45*)

Local

Tenderness

2 (6%)

28 (93%)

44 (98%)

Pain

1 (3%)

13 (43%)

25 (56%)

Induration

0

5 (17%)

8 (18%)

Erythema

0

1 (3%)

5 (11%)

Systemic

Malaise

1 (3%)

11 (37%)

11 (24%)

Headache

5 (16%)

8 (27%)

5 (11%)

Myalgia

0

2 (7%)

1 (2%)

Nausea

0

1 (3%)

1 (2%)

Diarrhea

0

0

1 (2%)

Feverish (subjective)

0

3 (10%)

2 (4%)

Fever ≥ 100°F

1 (3%)

0

1 (2%)

Vomiting

0

0

0

* At 27 or 34 months following a previous dose given in
different studies.

Solicited Injection Site And Systemic Reactions When
Given With Menactra Vaccine

The majority (70%-77%) of solicited injection site
reactions at the Typhim Vi and at the Menactra injection sites were reported as
Grade 1 and resolved within 3 days post-vaccination. The most common systemic
reactions were headache (41% when Menactra and Typhim Vi were given concomitantly;
42% when Typhim Vi was given with Placebo, and 33% when Menactra vaccine was
given alone one month after Typhim Vi vaccination) and fatigue (38% when
Menactra vaccine and Typhim Vi were given concomitantly; 35% when Typhim Vi was
given with Placebo, and 27% when Menactra vaccine was given alone one month
after Typhim Vi vaccination). Fever > 40.0°C and seizures were not reported.

Data From Worldwide Post-Marketing Experience

In addition to reports in clinical trials, worldwide
voluntary adverse events reports received since market introduction of Typhim
Vi vaccine are listed below. This list includes serious events and/or events
which were included based on severity, frequency of reporting or a plausible
causal connection to Typhim Vi vaccine. Because these events were reported
voluntarily from a population of uncertain size, it is not possible to reliably
estimate their frequency or establish a causal relationship to vaccination.

Musculoskeletal And Connective Tissue Disorders

Nervous System Disorders

Respiratory System Disorders

Additional Adverse Events

Post-marketing reports of glomerulonephritis,
neutropenia, bilateral retinitis, and polyarthritis have been reported in
patients who had also received other vaccines; however, a causal relationship
has not been established.

Reporting Of Adverse Events

Reporting by parents and patients of all adverse events
occurring after vaccine administration should be encouraged. Adverse events
following immunization with vaccine should be reported by the health-care
provider to the US Department of Health and Human Services (DHHS) Vaccine
Adverse Event Reporting System (VAERS). Reporting forms and information about reporting
requirements or completion of the form can be obtained from VAERS through a tollfree
number 1-800-822-7967 or visit the VAERS website at http//www.vaers.org.17

DRUG INTERACTIONS

There are no known interactions of Typhim Vi vaccine with
drugs or foods.

Concomitant Vaccine Administration

Typhim Vi was concomitantly administered with Menactra
vaccine in individuals 18 through 55 years of age (see CLINICAL PHARMACOLOGY
and ADVERSE REACTIONS).

No studies have been conducted in the US to evaluate
interactions or immunological interference between the concurrent use of Typhim
Vi vaccine and drugs (including antibiotics and antimalarial drugs), immune
globulins or other vaccines (including common travelers vaccines such as
tetanus, poliomyelitis, hepatitis A, and yellow fever).

Typhim Vi vaccine must not be mixed with any vaccine in
the same syringe. Separate injection sites should be used in case of
concomitant administration.

Carcinogenesis, Mutagenesis, Impariment Of Fertility

Typhim Vi vaccine has not been evaluated for its
carcinogenic potential, mutagenic potential or impairment of fertility.

Pregnancy Category C

Animal reproduction studies have not been conducted with
Typhim Vi vaccine. It is not known whether Typhim Vi vaccine can cause fetal
harm when administered to a pregnant woman or can affect reproduction capacity.
Typhim Vi vaccine should be given to a pregnant woman only if clearly needed.14

When possible, delaying vaccination until the second or
third trimester to minimize the possibility of teratogenicity is a reasonable
precaution.18

Nursing Mothers

It is not known whether Typhim Vi vaccine is excreted in
human milk. Because many drugs are excreted in human milk, caution should be
exercised when Typhim Vi vaccine is administered to a nursing woman.

There is no data on the use of this product in nursing
mothers.

Pediatric Use

Safety and effectiveness of Typhim Vi vaccine have been
established in children 2 years of age and older.10,11 (See DOSAGE
AND ADMINISTRATION section.) FOR CHILDREN BELOW THE AGE OF 2 YEARS, SAFETY
AND EFFECTIVENESS HAVE NOT BEEN ESTABLISHED.